Transcriptomics of type 2 diabetic and healthy human neutrophils.
Transcriptomics of type 2 diabetic and healthy human neutrophils.
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DOI：
10.1186/s12865-021-00428-6
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发表时间：
2021-06-16
期刊：
影响因子：
3
通讯作者：
Freire M
中科院分区：
文献类型：
--
作者：
Kleinstein SE;McCorrison J;Ahmed A;Hasturk H;Van Dyke TE;Freire M
慢性炎症性疾病，包括糖尿病和心血管疾病，是异质性的，往往是共病的，全球患病率不断上升。不受控制的2型糖尿病（T2 D）可导致严重的炎症并发症。由于中性粒细胞对正常和异常炎症至关重要，我们进行了RNA-seq转录组学分析，以研究中性粒细胞基因表达与T2 D表型之间的关联。由于专门的促消退脂质介质（SPM）作用于消退炎症，我们进一步研究了中性粒细胞受体结合SPM消退素E1（RvE 1）对分离的糖尿病和健康中性粒细胞的影响。对来自N = 11个T2 D和N = 7个具有可用临床数据的健康个体的中性粒细胞进行细胞分离和RNA-seq分析。此外，在RNA-seq之前，培养的嗜中性粒细胞（N = 3 T2 D，N = 3健康）被增加的RvE 1剂量（0 nM、1 nM、10 nM或100 nM）干扰。通过生物信息学管道评估数据，包括途径分析和事后错误发现率（FDR）校正。我们观察到T2 D和健康中性粒细胞之间50个基因的显著差异表达（p < 0.05），包括炎症和脂质相关基因SLC 9A 4、NECTIN 2和PLPP 3中T2 D基因表达的降低（p < 0.003）。RvE 1处理诱导了各组间剂量依赖性差异基因表达（未校正的p < 0.05），包括59个健康和216个T2 D嗜中性粒细胞基因。将T2 D与健康中性粒细胞进行比较，在RvE 1剂量下有1097个基因差异表达，包括参与炎症的两个重要基因LILRB 5和AKR 1C 1（p < 0.05）。中性粒细胞转录组数据库揭示了新的慢性炎症和脂质相关基因，与对照组相比，T2 D细胞之间差异表达，细胞对RvE 1的反应呈剂量依赖性，基因表达变化。揭示糖尿病中性粒细胞反应异常的调节机制可能会导致更好的诊断和治疗，靶向炎症和炎症解决。在线版本包含补充材料，可通过10.1186/s12865-021-00428-6获得。
Chronic inflammatory diseases, including diabetes and cardiovascular disease, are heterogeneous and often co-morbid, with increasing global prevalence. Uncontrolled type 2 diabetes (T2D) can result in severe inflammatory complications. As neutrophils are essential to normal and aberrant inflammation, we conducted RNA-seq transcriptomic analyses to investigate the association between neutrophil gene expression and T2D phenotype. As specialized pro-resolving lipid mediators (SPM) act to resolve inflammation, we further surveyed the impact of neutrophil receptor binding SPM resolvin E1 (RvE1) on isolated diabetic and healthy neutrophils. Cell isolation and RNA-seq analysis of neutrophils from N = 11 T2D and N = 7 healthy individuals with available clinical data was conducted. Additionally, cultured neutrophils (N = 3 T2D, N = 3 healthy) were perturbed with increasing RvE1 doses (0 nM, 1 nM, 10 nM, or 100 nM) prior to RNA-seq. Data was evaluated through a bioinformatics pipeline including pathway analysis and post hoc false discovery rate (FDR)-correction. We observed significant differential expression of 50 genes between T2D and healthy neutrophils (p < 0.05), including decreased T2D gene expression in inflammatory- and lipid-related genes SLC9A4, NECTIN2, and PLPP3 (p < 0.003). RvE1 treatment induced dose-dependent differential gene expression (uncorrected p < 0.05) across groups, including 59 healthy and 216 T2D neutrophil genes. Comparing T2D to healthy neutrophils, 1097 genes were differentially expressed across RvE1 doses, including two significant genes, LILRB5 and AKR1C1, involved in inflammation (p < 0.05). The neutrophil transcriptomic database revealed novel chronic inflammatory- and lipid-related genes that were differentially expressed between T2D cells when compared to controls, and cells responded to RvE1 dose-dependently by gene expression changes. Unraveling the mechanisms regulating abnormalities in diabetic neutrophil responses could lead to better diagnostics and therapeutics targeting inflammation and inflammation resolution. The online version contains supplementary material available at 10.1186/s12865-021-00428-6.